This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The mucosal surface of the oral cavity interfaces with the external environment, and hosts a complex flora of commensal and pathogenic microorganisms. Salivary secretions play a central role in maintaining oral health through innate immune mechanisms, including epithelial-derived host defense peptides (HDPs). Oral epithelia, including human gingiva and salivary glands, express beta-defensin and cathelicidin HDPs. Infectious and inflammatory stressors can alter mucosal immune parameters, and influence epithelial HDP expression in health and disease. We propose that an untraditional model species likely possess more potent and/or broader repertoires of HDPs consequent to individuals living under more extreme environmental conditions. The African Spotted Hyena (Crocuta crocuta) exhibits unique wound-healing capabilities, and survives successfully on a diet containing extreme microbial loads. Studies on Innate immune defense of species with remarkably low susceptibility to infectious diseases may provide molecular templates for development of novel biotherapeutics. Our long-term goal is to understand how antimicrobial and immunomodulatory activities of hyena HDPs can be applied towards development of novel immunotherapeutics and potent, antibiotics. The objective is to perform a comparative salivary gland transcriptome and peptidome analysis in wild versus captive spotted hyenas. Our hypothesis is that the immunological robustness in the hyena is explained by broad-spectrum antimicrobial and immunomodulatory activity of epithelial-derived HDPs. The rationale for the proposed is that understanding the basis for the heightened microbicidal activity of wild-living hyena saliva is expected to provide exploitable clues regarding how to improve human oral health.